Abstract Delirium (acute brain dysfunction) is a common complication of critical care and a significant patient safety problem, occurring in up to two-thirds of patients in the intensive care unit (ICU). ICU delirium is independently associated with increased mortality and morbidity, predicts functional decline, and raises health care costs. Therapeutic interventions for ICU delirium (such as optimizing sedation management, daily awakening and breathing trials for patients on ventilators, formal delirium monitoring, and early mobility) have been developed and individually demonstrated to be effective in producing clinical benefits across a range of populations and critical care settings. In spite of evidence supporting these practices, their widespread implementation has been challenging, limiting the potential reduction in iatrogenic harm if they were applied consistently. The impact of deploying specific care processes for ICU delirium in a coordinated bundle on practice adoption, clinical outcomes, and program sustainability has not been examined. This project is designed to help fill that knowledge gap. We propose three aims that will address commonly encountered practice adoption barriers, provide information on models for accelerated implementation of an important patient safety intervention, and maximize spread of study findings with a practical dissemination strategy. Aim 1: To implement a standardized set of care interventions targeting the prevention and amelioration of ICU delirium as an integrated, interdisciplinary bundle (the ABCDE bundle) for critically ill patients in ICUs across 3 different hospital environments (large tertiary center, community, rural) in the Baylor Health Care System (BHCS), using a multifaceted approach to promote bundle uptake. Sites will use three common elements to achieve implementation: i) physician and nursing ABCDE bundle champions; ii) deployment of clinical decision and workflow support tools; and iii) timely feedback on performance of care processes in the bundle. Aim 2: To evaluate the impact of the ABCDE bundle implementation program on quantitative and qualitative outcomes using mixed-methods analyses. We will assess practice adoption, clinical, and program cost outcomes pre- and post-ABCDE intervention, comparing these results with a group of concurrent BHCS control hospitals not receiving the implementation program. Qualitative analyses will explore quality improvement culture and strategies at organizational and local levels, as well as contextual variables related to diffusion of the ABCDE bundle innovation. Aim 3: To disseminate project findings, methodology, and tools for ABCDE bundle implementation. We will build a structured implementation toolkit according to lessons learned from Aims 1 and 2 and partner with the Society of Hospital Medicine (SHM) to develop an implementation resource hosted on the SHM website. The toolkit and web-resource will be optimized based on feedback from local spread to BHCS hospitals not involved in the implementation program and external vetting by SHM experts. The final toolkit will be distributed to health care professional organizations and media sites.